Interaction between norepinephrine, NPY and VIP in the ovarian artery.

The in vitro effect and the interaction between norepinephrine (NE), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were studied in dissected segments of the rabbit ovarian artery. In addition, the structural requirement of the NPY receptor was investigated using NPY peptide analogs. NE induced a dose-dependent vasoconstriction with an Emax of 131.4 +/- 2.9% of K(+)-induced constriction. The vasoconstrictor effect of NPY was less than 5% of K(+)-induced vasoconstriction. Incubation of the artery with 10(-7) M NPY for 4 min induced a significant potentiation of NE-induced contractions. The selective NPY Y1 receptor agonist [Leu31, Pro34]NPY was also able to potentiate the NE response at the half-maximum contraction level, but not NPY(11-36), an NPY peptide fragment predominantly stimulating the NPY Y2 receptor. NPY exerted a dose-dependent vasoconstrictor effect on vessels contracted for 20 min with 10(-6) M NE. VIP induced a dose-dependent relaxation of vessels contracted with 10(-6) M NE. The VIP-induced relaxation could be reversed by NPY. In conclusion, receptors capable of interacting with NPY, presumably of the Y1 type, and VIP are present in the rabbit ovarian artery, and activation of these receptors may profoundly influence the response of the artery to norepinephrine.     

Comparison of helodermin, VIP and PHI in pancreatic secretion and blood flow in dogs

Helodermin, VIP and PHI, which share a high degree of homology with secretin, have been identified in the gut but their physiological role is unknown. In this study 3 series of tests were carried out to determine the actions of helodermin, VIP and PHI on pancreatic secretion in 6 conscious dogs and amylase release from the dispersed canine pancreatic acini and to correlate the alterations in pancreatic secretory and circulatory effects in 24 anesthetized dogs. Helodermin, VIP and PHI infused i.v. in graded doses (12.5-200 pmol/kg.h) resulted in a dose-dependent increase in pancreatic HCO3 secretion reaching, respectively, 100%, 7% and 2% of secretin maximum. When combined with constant dose infusion of CCK-8 (100 pmol/kg.h), helodermin but not VIP or PHI augmented dose-dependently the HCO3 secretion. When added in various concentrations (10(-10)-10(-5)M) to the incubation medium of dispersed pancreatic acini only helodermin but not VIP or PHI increased dose-dependently amylase release reaching about 50% of CCK-8 maximum. In anesthetized dogs, the pancreatic blood flow (PBF) measured by electromagnetic blood flowmetry showed an immediate and dose-dependent increase following the injections of various doses of helodermin, VIP, PHI and secretin, the peak blood flow preceding by about 1 min the peak secretory stimulation. This study shows that helodermin resembles secretin in its potent pancreatic HCO3 stimulation but differs from VIP or PHI which are poor secretagogues but potent vasodilators. We conclude that if tested peptides are released in the gut, helodermin, like secretin, may be involved in the hormonal stimulation of exocrine pancreas, whereas VIP and PHI may serve mainly as vasodilators in the pancreatic circulation.     

NPY and the regulation of behavioral development

Neuropeptide Y is implicated in the regulation of feeding in vertebrates, but recent studies in transgenic mice are contradictory. In this issue of Neuron, Wu et al. show a dual role for the Drosophila NPY (dNPF) in the developmental regulation of larval foraging and social behaviors, demonstrating a conserved role for this peptide in complex behaviors.     

Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters

Astrocytes in the brain release transmitters that actively modulate neuronal excitability and synaptic efficacy. Astrocytes also release vasoactive agents that contribute to neurovascular coupling. As reviewed in this article, Müller cells, the principal retinal glial cells, modulate neuronal activity and blood flow in the retina. Stimulated Müller cells release ATP which, following its conversion to adenosine by ectoenzymes, hyperpolarizes retinal ganglion cells by activation of A1 adenosine receptors. This results in the opening of G protein-coupled inwardly rectifying potassium (GIRK) channels and small conductance Ca²⁺-activated K⁺ (SK) channels. Tonic release of ATP also contributes to the generation of tone in the retinal vasculature by activation of P2X receptors on vascular smooth muscle cells. Vascular tone is lost when glial cells are poisoned with the gliotoxin fluorocitrate. The glial release of vasoactive metabolites of arachidonic acid, including prostaglandin E₂ (PGE₂) and epoxyeicosatrienoic acids (EETs), contributes to neurovascular coupling in the retina. Neurovascular coupling is reduced when neuronal stimulation of glial cells is interrupted and when the synthesis of arachidonic acid metabolites is blocked. Neurovascular coupling is compromised in diabetic retinopathy owing to the loss of glial-mediated vasodilation. This loss can be reversed by inhibiting inducible nitric oxide synthase. It is likely that future research will reveal additional important functions of the release of transmitters from glial cells.     

Nonlinear interactions in renal blood flow regulation

We have developed a model of tubuloglomerular feedback (TGF) and the myogenic mechanism in afferent arterioles to understand how the two mechanisms are coupled. This paper presents the model. The tubular model predicts pressure, flow, and NaCl concentration as functions of time and tubular length in a compliant tubule that reabsorbs NaCl and water; boundary conditions are glomerular filtration rate (GFR), a nonlinear outflow resistance, and initial NaCl concentration. The glomerular model calculates GFR from a change in protein concentration using estimates of capillary hydrostatic pressure, tubular hydrostatic pressure, and plasma flow rate. The arteriolar model predicts fraction of open K channels, intracellular Ca concentration (Ca(i)), potential difference, rate of actin-myosin cross bridge formation, force of contraction, and length of elastic elements, and was solved for two arteriolar segments, identical except for the strength of TGF input, with a third, fixed resistance segment representing prearteriolar vessels. The two arteriolar segments are electrically coupled. The arteriolar, glomerular, and tubular models are linked; TGF modulates arteriolar circumference, which determines vascular resistance and glomerular capillary pressure. The model couples TGF input to voltage-gated Ca channels. It predicts autoregulation of GFR and renal blood flow, matches experimental measures of tubular pressure and macula densa NaCl concentration, and predicts TGF-induced oscillations and a faster smaller vasomotor oscillation. There are nonlinear interactions between TGF and the myogenic mechanism, which include the modulation of the frequency and amplitude of the myogenic oscillation by TGF. The prediction of modulation is confirmed in a companion study (28).     

Frequency encoding in renal blood flow regulation

With a model of renal blood flow regulation, we examined consequences of tubuloglomerular feedback (TGF) coupling to the myogenic mechanism via voltage-gated Ca channels. The model reproduces the characteristic oscillations of the two mechanisms and predicts frequency and amplitude modulation of the myogenic oscillation by TGF. Analysis by wavelet transforms of single-nephron blood flow confirms that both amplitude and frequency of the myogenic oscillation are modulated by TGF. We developed a double-wavelet transform technique to estimate modulation frequency. Median value of the ratio of modulation frequency to TGF frequency in measurements from 10 rats was 0.95 for amplitude modulation and 0.97 for frequency modulation, a result consistent with TGF as the modulating signal. The simulation predicted that the modulation was regular, while the experimental data showed much greater variability from one TGF cycle to the next. We used a blood pressure signal recorded by telemetry from a conscious rat as the input to the model. Blood pressure fluctuations induced variability in the modulation records similar to those found in the nephron blood flow results. Frequency and amplitude modulation can provide robust communication between TGF and the myogenic mechanism.     

Venular-arteriolar communication in the regulation of blood flow

Muscle blood flow is regulated to meet the metabolic needs of the tissue. With the vasculature arranged as a successive branching of arterioles and the larger, >50 microm, arterioles providing the major site of resistance, an increasing metabolic demand requires the vasodilation of the small arterioles first then the vasodilation of the more proximal, larger arterioles. The mechanism(s) for the coordination of this ascending vasodilation are not clear and may involve a conducted vasodilation and/or a flow-dependent response. The close arteriolar-venular pairing provides an additional mechanism by which the arteriolar diameter can be increased due to the diffusion of vasoactive substances from the venous blood. Evidence is presented that the venular endothelium releases a relaxing factor, a metabolite of arachidonic acid, that will vasodilate the adjacent arteriole. The stimulus for this release is not known, but it is hypothesized that hypoxia-induced ATP release from red blood cells may be responsible for the stimulation of arachidonic release from the venular endothelial cells. Thus the venous circulation is in an optimal position to monitor the overall metabolic state of the tissue and thus provide a feedback regulation of arteriolar diameter.     

Roles of nuclear NPY and NPY receptors in the regulation of the endocardial endothelium and heart function

It is now well accepted that the heart is a multifunctional organ in which endothelial cells, and more particularly endocardial endothelial cells (EECs), seem to play an important role in regulating and maintaining cardiac excitation-contraction coupling. Even if major differences exist between vascular endothelial cells (VECs) and EECs, all endothelial cells including EECs release a variety of auto- and paracrine factors such as nitric oxide, endothelin-1, angiotensin II, and neuropeptide Y. All these factors were reported to affect cardiomyocyte contractile performance and rhythmicity. In this review, findings on the morphology of EECs, differences between EECs and other types of endothelial cells, interactions between EECs and the adjacent cardiomyocytes, and effects of NPY on the heart will be presented. We will also show evidence on the presence and localization of NPY and the Y1 receptor in the endocardial endothelium and discuss their role in the regulation of cytosolic and nuclear free calcium.     

Update on adipose tissue blood flow regulation

According to Fick's principle, any metabolic or hormonal exchange through a given tissue depends on the product of the blood flow to that tissue and the arteriovenous difference. The proper function of adipose tissue relies on adequate adipose tissue blood flow (ATBF), which determines the influx and efflux of metabolites as well as regulatory endocrine signals. Adequate functioning of adipose tissue in intermediary metabolism requires finely tuned perfusion. Because metabolic and vascular processes are so tightly interconnected, any disruption in one will necessarily impact the other. Although altered ATBF is one consequence of expanding fat tissue, it may also aggravate the negative impacts of obesity on the body's metabolic milieu. This review attempts to summarize the current state of knowledge on adipose tissue vascular bed behavior under physiological conditions and the various factors that contribute to its regulation as well as the possible participation of altered ATBF in the pathophysiology of metabolic syndrome.     

The role of the ovarian horn locus in regulation of spontaneous electric activity of myometrial rhythmogenic areas

The role of the ovarian area of the uterine horn in coordination of spontaneous activity of myometrial rhythmogenic areas was studied in nonpregnant rats both under normal conditions and following transection of the uterine horn in its middle part to isolate the ovarian locus from the distally located uterine active areas. The effect of oxytocin as a factor that reveals a leading role of the ovarian locus in synchronization of myometrial spontaneous activity was studied under the above conditions. Intravenous oxytocin administration (10^–1 μg/kg) under normal conditions promotes a considerable increase in the peak amplitude and mean rise rate in all the three rhythmogenic areas (%; ovarian horn area—by 148.63 ± 6.1, p ≤ 0.001 and 141.04 ± 7.6, p ≤ 0.01; cervical horn area—by 143.85 ± 3.5, p ≤ 0.001 and 146.89 ± 8.5, p ≤ 0.001; uterine corpus—by 146.20 ± 7.2, p ≤ 0.001 and 139.73 ± 8.2, p ≤ 0.05, respectively). Under the same conditions, also there is a similar increase in the active state duration in all the three areas (%; 132.70 ± 4.5, p ≤ 0.05; 124.90 ± 9.6, p ≤ 0.05; 128.03 ± 7.2, p ≤ 0.05, respectively). Following transection of the uterine horn, oxytocin administration causes an increase in all the three activity indicators only in the ovarian horn area (%; 134.86 ± 2.5, p ≤ 0.05; 139.49 ± 4.5, p ≤ 0.001; 123.8 ± 7.3, p ≤ 0.05, respectively). In the cervical horn area and uterine corpus, no appreciable changes in these indicators were detected under both conditions. We believe that the ovarian locus is involved in coordination of activities of all the three myometrial rhythmogenic areas as revealed by oxytocin.     

Morphologic aspects of local blood flow regulation in the myocardium

In 67 preparations of the human hearts at the first and second periods of mature age, spatial interrelations between blood vessels and cardiac muscle fibers in the ventricle myocardium have been studied. All the elements of the myocardial blood bed are oriented under a certain angle in relation to the cardiac muscle fibers. Regular arrangement of the arteries and sinusoid dilated veins under endocardium on the top of the papillary muscles and in the muscular trabecules is demonstrated. As proves the mathematical model, the slope orientation of the blood bed elements towards the cardiac muscle fibers ensures and adequate realization of the external influence of the contractile cardiomyocytes to the successive movement of blood along the intramural myocardial vessels. From morphological positions, a conclusion on the mechanism of the intracavitary pressure effect on blood movement along the intramural veins of the ventricular myocardium is argued. A conclusion is made on the leading role of the extravascular factors (intramyocardial and intercavitary pressure) in the local regulation of the blood stream in the myocardium and in development of working cardiac hyperemia.